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Chapter 4 : Cytokines and Epithelial Function

Authors: Sean P. Colgan1, Glenn T. Furuta2, Cormac T. Taylor3
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Affiliations: 1: Center for Experimental Therapeutics, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115; 2: Combined Program in Pediatric Gastroenterology and Nutrition, Children's Hospital, Harvard Medical School, Boston, MA 02114; 3: Department of Medicine and Therapeutics, The Conway Institute, University College, Dublin, Ireland
Content Type: Monograph
Publication Year: 2003

Category: Clinical Microbiology

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Abstract:

This chapter talks about recent literature with regard to epithelial cytokine responses, with particular emphasis on functional consequences. It discusses the direct consequences of cytokines on aspects of epithelial function. An interesting exception with regard to cytokine influences on ion transport is that of interleukin-4 (IL-4) and IL-13. While these cytokines share common receptor subunits and in most cases display overlapping functions (e.g., attenuation of barrier function), only IL-4 appears to influence electrogenic chloride secretion. This finding was one of the first divergent functions ascribed to these apparently redundant cytokines, although recent studies suggest no differences between IL-4 and IL-13 with regard to proximal receptor activation. Recent work suggests that blockade of interaction with the cytoskelton using the polyamine cadaverine severely abrogates epithelial signaling to polymorpho-nuclear leukocyte (PMN). In the intestine, cytokine influences on epithelial function may best be exemplified through the study of enteric infections, specifically related to acute responses following initial microorganism-epithelial interaction.

Citation: Colgan S, Furuta G, Taylor C. 2003. Cytokines and Epithelial Function, p 61-78. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch4

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Cytokines and Epithelial Function
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Citation: Colgan S, Furuta G, Taylor C. 2003. Cytokines and Epithelial Function, p 61-78. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch4
/content/10.1128/9781555817848.chap4.fig4-1
FIGURE 1

Epithelial-derived TNF-α synergizes with IFN-γ in an autocrine manner. In response to a number of stimuli, including bacterial invasion and hypoxia, epithelial cells become a source of TNF-α. The polarized release (basolateral) of TNF-α synergizes with immune-derived cytokines, especially IFN-γ, resulting in influences on a number of epithelial functions, including decreased barrier function, diminished electrogenic chloride secretion, induction of MHC molecules, and liberation of proinflammatory chemokines.

10.1128/9781555817848/fig4-1_thmb.gif
10.1128/9781555817848/fig4-1.gif
Image of FIGURE 1
FIGURE 1

Epithelial-derived TNF-α synergizes with IFN-γ in an autocrine manner. In response to a number of stimuli, including bacterial invasion and hypoxia, epithelial cells become a source of TNF-α. The polarized release (basolateral) of TNF-α synergizes with immune-derived cytokines, especially IFN-γ, resulting in influences on a number of epithelial functions, including decreased barrier function, diminished electrogenic chloride secretion, induction of MHC molecules, and liberation of proinflammatory chemokines.

Citation: Colgan S, Furuta G, Taylor C. 2003. Cytokines and Epithelial Function, p 61-78. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch4
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FIGURE 2

Phases of cytokine actions on acute epithelial infection. Epithelial cells are central to the coordinated response to microorganism infection (phase 1). Rapid induction and release of PMN chemokines (phase 2) elicit the accumulation of PMN within and across the epithelial surface. PMN at the lumenal surface initiates a Cl− secretory response and fluid transport which functionally flushes the surface of the epithelium. In phase 3 of the response, epithelial-derived cytokines (e.g., TNF-α) synergize with cytokines liberated in the intraepithelial and lamina propria compartments (e.g., IFN-γ) to attenuate fluid transport. In phase 4, intraepithelial and lamina propria lymphocyte-derived cytokines (e.g., IFN-γ, IL-4, and IL-13) induce epithelial lipoxin receptors, the ligation of which results in attenuation of PMN accumulation. In phase 5, lipoxin-induced epithelial BPI provides a protective antimicrobial action for the resolution of acute inflammation.

10.1128/9781555817848/fig4-2_thmb.gif
10.1128/9781555817848/fig4-2.gif
Image of FIGURE 2
FIGURE 2

Phases of cytokine actions on acute epithelial infection. Epithelial cells are central to the coordinated response to microorganism infection (phase 1). Rapid induction and release of PMN chemokines (phase 2) elicit the accumulation of PMN within and across the epithelial surface. PMN at the lumenal surface initiates a Cl− secretory response and fluid transport which functionally flushes the surface of the epithelium. In phase 3 of the response, epithelial-derived cytokines (e.g., TNF-α) synergize with cytokines liberated in the intraepithelial and lamina propria compartments (e.g., IFN-γ) to attenuate fluid transport. In phase 4, intraepithelial and lamina propria lymphocyte-derived cytokines (e.g., IFN-γ, IL-4, and IL-13) induce epithelial lipoxin receptors, the ligation of which results in attenuation of PMN accumulation. In phase 5, lipoxin-induced epithelial BPI provides a protective antimicrobial action for the resolution of acute inflammation.

Citation: Colgan S, Furuta G, Taylor C. 2003. Cytokines and Epithelial Function, p 61-78. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch4
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